WO2017107242A1 - Composition pharmaceutique, procédé de préparation associé et application associée - Google Patents

Composition pharmaceutique, procédé de préparation associé et application associée Download PDF

Info

Publication number
WO2017107242A1
WO2017107242A1 PCT/CN2015/100130 CN2015100130W WO2017107242A1 WO 2017107242 A1 WO2017107242 A1 WO 2017107242A1 CN 2015100130 W CN2015100130 W CN 2015100130W WO 2017107242 A1 WO2017107242 A1 WO 2017107242A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
cycloserine
capsule
amount
mesh
Prior art date
Application number
PCT/CN2015/100130
Other languages
English (en)
Chinese (zh)
Inventor
陈日星
陈建豪
罗盛莲
范红银
陈万英
郝小妹
Original Assignee
广州瑞尔医药科技有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 广州瑞尔医药科技有限公司 filed Critical 广州瑞尔医药科技有限公司
Publication of WO2017107242A1 publication Critical patent/WO2017107242A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/485—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds

Definitions

  • the invention relates to the technical field of pharmaceutical preparations, in particular to a pharmaceutical composition and a preparation method and application thereof.
  • Tuberculosis is a disease affecting people's health in tuberculosis. With the emergence of anti-tuberculosis drugs such as streptomycin and isoniazid, tuberculosis has become a treatable disease. However, due to the lack of relevant knowledge and the irregular treatment, the drug resistance of Mycobacterium tuberculosis has become more and more serious.
  • Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis. Among the three diseases that need to be controlled by the World Health Organization, tuberculosis is second only to AIDS. China is a country with a serious tuberculosis epidemic. In addition, with the resistance of tuberculosis, China's drug-resistant patients are also increasing. Therefore, the development of anti-tuberculosis drugs, especially anti-tuberculosis drugs are very necessary.
  • cycloserine is mainly used to treat tuberculosis caused by drug-resistant tuberculosis.
  • cycloserine can also be used to treat other diseases.
  • the use of cycloserine for the treatment of psychosis, depression or Alzheimer's disease is disclosed in US Patent No. US2014018349, World Intellectual Property Patent WO2008118785, European Patent No. EP 2 338 482, and European Patent No. EP 0 378 134.
  • U.S. Patent No. 2014,213,621 discloses the use of cycloserine for the treatment of chronic pain.
  • the preparation of the existing cycloserine is mainly an immediate release preparation, the composition has a small particle size, the D 90 particle size is less than 64 ⁇ m, the stability of the preparation is relatively poor, and the seal is sealed under accelerated conditions (temperature 40 ° C, humidity 75%). After 40 days of storage, the percentage of the labeled amount of the preparation was reduced from 99.1% to 43.3%, the degradation amount was accelerated to 56.3% for 40 days, and the sealed storage was accelerated for 180 days under accelerated conditions, and the main drug was almost completely degraded.
  • the percentage of the labeled amount of the preparation was reduced from 99.1% to 86.4%, and the degradation amount at room temperature for 180 days was 12.8%. Because the preparation is relatively unstable, it will affect the therapeutic effect and the safety of use.
  • Russian patent RU 2248205 discloses the addition of some fillers to cycloserine and filling in capsules to improve the fluidity of the contents of the capsules and the stability of the preparation, wherein the fillers added are mainly calcium phosphate dihydrate, silica gel and stearic acid. calcium.
  • the capsule increases the calcium phosphate dihydrate to increase the fluidity of the capsule contents, but since the frictional force of the calcium phosphate dihydrate is large, it is easy to wear the machine, and even causes a problem that the powder discolors quickly for a long time.
  • the patent does not have a specific test value to show its stability.
  • the preparation prepared according to the patent prescription is still inferior in stability, and is sealed and stored for 180 days under accelerated conditions (temperature 40 ° C, humidity 75%).
  • the percentage of the amount decreased from 99.3% to 65.4%, and the accelerated amount of degradation in 180 days was 34.1%.
  • Under normal temperature conditions temperature 25 ° C, humidity 60%
  • the storage was sealed for 180 days, the percentage of the labeled amount of the preparation was reduced from 99.3% to 94.8%, and the degradation amount at room temperature for 180 days was 4.5%.
  • the prescription found that there is a problem of discoloration of the content in the stability test, which may be related to the fact that the metal particles in the wear of the mold are brought into the content, thereby accelerating the degradation of the active ingredient, and the patent does not solve the problem that the stability of the variety is not good.
  • the problem has not been found to have a patent that publicly increases the stability of the cycloserine formulation.
  • a pharmaceutical composition comprising cycloserine and an adjuvant, said pharmaceutical composition having a D 90 particle size of from 75 to 380 ⁇ m, said adjuvant being used in an amount of from 9 to 45% by weight based on the total mass of the pharmaceutical composition.
  • the excipient comprises talc, and a binder and/or compressible excipient.
  • the talc is used in an amount of 9 to 45% by weight based on the total amount of the pharmaceutical composition
  • the binder is used in an amount of 0 to 6% based on the total mass of the pharmaceutical composition.
  • the amount used is from 0 to 16% of the total mass of the pharmaceutical composition.
  • the excipient comprises talc and a binder, the talc being used in an amount of from 23 to 38% by weight based on the total mass of the pharmaceutical composition, and the amount of the binder being based on the total mass of the pharmaceutical composition. 0.05 to 2%.
  • the excipient comprises talc and a compressible adjuvant
  • the talc is used in an amount of 23 to 38% by weight of the total mass of the pharmaceutical composition
  • the compressive auxiliary is used in a total amount of the pharmaceutical composition. 8 to 14% of the mass.
  • the binder is selected from the group consisting of polyvinylpyrrolidone, hypromellose, hydroxypropylcellulose, ethylcellulose, methylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose
  • the compressible auxiliary material is one or more selected from the group consisting of lactose, starch, calcium hydrogen phosphate, microcrystalline cellulose, mannitol, and dextrin.
  • the pharmaceutical composition is in the form of a capsule, and the hollow capsule of the capsule is a gelatin hollow capsule or a hypromellose hollow capsule, and the hollow capsule has a loss on drying of ⁇ 15.0%.
  • Another object of the present invention is to provide a process for the preparation of the above pharmaceutical composition.
  • the preparation method of the above pharmaceutical composition comprises the following steps:
  • the cycloserine having a D 90 particle size of 75-380 ⁇ m and the auxiliary material are uniformly mixed according to the mass percentage, thereby obtaining the pharmaceutical composition;
  • the cycloserine and the auxiliary material are mixed according to the mass percentage, and then subjected to wet granulation, dry granulation or fluidized bed granulation, dried, and sieved to obtain the pharmaceutical composition;
  • the cycloserine is mixed in the above percentage by mass to obtain the pharmaceutical composition.
  • the pharmaceutical composition has a loss on drying of from 0.2 to 2% and a D 90 particle size of from 120 to 380 ⁇ m.
  • Another object of the invention is to provide the use of the above pharmaceutical compositions.
  • the above pharmaceutical composition is used in the preparation of a medicament for treating psychosis, depression, Alzheimer's disease or chronic pain.
  • the present invention is directed to the deficiencies of the prior art, and provides a pharmaceutical composition of cycloserine, in particular, an immediate release capsule containing cycloserine.
  • the current cycloserine preparation is mainly a capsule, but the stability of the preparation is poor.
  • the degradation of the main drug in the preparation under normal temperature conditions (temperature 25 ° C, humidity 60%) and accelerated conditions (40 ° C, humidity 75%) Fast, affecting the efficacy of the preparation and the safety of use.
  • the present invention not only increases the rate of release of the formulation by increasing the particle size of the excipient (and thereby increasing the particle size of the pharmaceutical composition) and controlling the amount of dry weight loss of the pharmaceutical composition, but also greatly enhances the stability of the formulation.
  • the pharmaceutical composition of the present invention has a D 90 particle size of from 75 to 380 ⁇ m and a loss on drying of from 0.2 to 2%.
  • the pharmaceutical composition of the present invention can control the D 90 particle diameter of the pharmaceutical composition to 75-380 ⁇ m by adding an auxiliary material to the cycloserine or combining the cycloserine with the auxiliary material, thereby not only making the capsule content have good fluidity. As well as lubricity, it also increases the release rate of the formulation and the stability of the formulation.
  • the excipients in the prescription are mainly talc, as well as binders and/or compressible excipients.
  • the pharmaceutical composition of the present invention is in the form of a capsule, and the hollow capsule of the capsule is a gelatin hollow capsule or a hypromellose hollow capsule, and the hollow capsule has a loss on drying of ⁇ 15.0%.
  • the stability of the pharmaceutical composition of the present invention is greatly improved compared with the prior art, and the optimal example is at normal temperature (temperature 25 ° C, Humidity 60%) sealed for 180 days, the amount of degradation of the indicated amount of the formulation is ⁇ 0.5%, sealed for 180 days under accelerated conditions (40 ° C, humidity 75%), and the amount of degradation of the indicated amount of the formulation ⁇ 4.0%.
  • the cyclic serine accounted for 90.9% of the total, the cycloserine content was 99.713%, and the talc powder was 325 mesh (particle size 44 ⁇ m).
  • the capsule prepared by the above method had a loss on drying of 0.769%, a disintegration time in water of 5 minutes, and a dissolution rate of more than 90% at pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, and the talc powder was 325 mesh.
  • the capsule prepared by the above method had a loss on drying of 0.521%, a disintegration time in water of 5 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounted for 55.6% of the total, the cycloserine content was 99.713%, and the talc powder was 325 mesh.
  • the capsule prepared by the above method had a loss on drying of 0.672%, a disintegration time in water of 5 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.668%, and the talc powder was 325 mesh.
  • the capsule prepared by the above method had a loss on drying of 0.530%, a disintegration time in water of 5 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, and the talc powder was 200 mesh (particle size 75 ⁇ m).
  • the capsule prepared by the above method had a loss on drying of 0.496%, a disintegration time in water of 5 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, and the talc powder was 200 mesh.
  • the capsule prepared by the above method had a loss on drying of 0.583%, a disintegration time in water of 5 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cycloserine accounted for 64.1% of the total, the cycloserine content was 99.713%, and the talc powder was 100 mesh (particle size 150 ⁇ m).
  • the capsule prepared by the above method had a loss on drying of 0.578%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • Cycloserine accounted for 64.1% of the total, the content of cycloserine was 99.619%, and the talc powder was 100 mesh.
  • the capsule prepared by the above method had a loss on drying of 0.544%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the wet granulation excipient 100 mesh, the solvent was water, the binder accounted for 1.0% of the total, and the binder was polyvinylpyrrolidone K30.
  • the capsule prepared by the above method had a loss on drying of 1.201%, a disintegration time of 4 minutes in water, and a dissolution rate of more than 90% at pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the wet granulation excipient 60 mesh (particle size 250 ⁇ m), the solvent was water, the binder accounted for 1.0% of the total, and the binder was polyvinylpyrrolidone K30.
  • the capsule prepared by the above method had a loss on drying of 1.015%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the cyclic serine accounts for 64.1% of the total, the cycloserine content is 99.713%, the wet granulation auxiliary material is 60 mesh, the solvent is water, the binder accounts for 1.0% of the total, and the binder is polyvinylpyrrolidone K30.
  • the capsule prepared by the above method had a loss on drying of 2.183%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounted for 90.9% of the total, the cycloserine content was 99.713%, the wet granulation adjuvant 40 mesh (particle size 380 ⁇ m), the solvent was water, the binder accounted for 0.25% of the total, and the binder was polyvinylpyrrolidone K30.
  • the capsule prepared by the above method had a loss on drying of 0.627%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the wet granulation auxiliary material was 60 mesh, the solvent was ethanol, the binder accounted for 1.0% of the total, and the binder was polyvinylpyrrolidone K30.
  • the capsule prepared by the above method had a loss on drying of 0.756%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the cyclic serine accounted for 55.6% of the total, the cycloserine content was 99.713%, the wet granulation auxiliary material was 60 mesh, the solvent was ethanol, the binder accounted for 1.0% of the total, and the binder was polyvinylpyrrolidone K30.
  • the capsule prepared by the above method had a loss on drying of 0.701%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the fluidized bed granulation auxiliary material was 60-80 mesh, the solvent was ethanol, the binder accounted for 1.0% of the total, and the binder was polyvinylpyrrolidone K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured as a polyvinylpyrrolidone K30 ethanol solution, and the prescribed amount of talc powder is placed in a fluidized bed and sprayed with polyvinylpyrrolidone K30 ethanol solution to prepare wet particles, and dried in a fluidized state. After 60-mesh to 80-mesh sieve, the prescribed amount of cycloserine was sieved through 100 mesh and mixed with the granulated excipients, and then the No. 1 gelatin hollow capsule was filled according to the specification of 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.723%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.474%, the wet granulation adjuvant was 60 mesh, the solvent was ethanol, the binder accounted for 1.0% of the total, and the binder was polyvinylpyrrolidone K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured into a polyvinylpyrrolidone K30 ethanol solution, and a prescribed amount of talc powder is added to the soft material, and the wet granules are sieved through 40 mesh, and dried at 60 ° C for 2 hours to dry the granules. After 60 mesh sieves, the granules after granulation were obtained.
  • the prescribed amount of cycloserine was passed through a 100 mesh sieve, and then mixed with the granulated auxiliary material, and the No. 1 gelatin hollow capsule was filled in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.635%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the wet granulation auxiliary material was 60 mesh, the solvent was ethanol, the binder accounted for 0.1% of the total amount, and the binder was polyvinylpyrrolidone K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured into a polyvinylpyrrolidone K30 ethanol solution, and a prescribed amount of talc powder is added to the soft material, and the wet granules are sieved through 40 mesh, and dried at 60 ° C for 2 hours to dry the granules. After 60 mesh sieves, the granules after granulation were obtained.
  • the prescribed amount of cycloserine was passed through a 100 mesh sieve, and then mixed with the granulated auxiliary material, and the No. 1 gelatin hollow capsule was filled in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.697%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the wet granulation auxiliary material was 60 mesh, the solvent was ethanol, the binder accounted for 3% of the total, and the binder was polyvinylpyrrolidone K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured into a polyvinylpyrrolidone K30 ethanol solution, and a prescribed amount of talc powder is added to the soft material, and the wet granules are sieved through 40 mesh, and dried at 60 ° C for 2 hours to dry the granules. After 60 mesh sieves, the granules after granulation were obtained.
  • the prescribed amount of cycloserine was passed through a 100 mesh sieve, and then mixed with the granulated auxiliary material, and the No. 1 gelatin hollow capsule was filled in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.640%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% at pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the wet granulation adjuvant 40 mesh, the solvent was ethanol, the binder accounted for 6% of the total, and the binder was polyvinylpyrrolidone K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured into a polyvinylpyrrolidone K30 ethanol solution, and a prescribed amount of talc powder is added to the soft material, and the wet granules are sieved through a 20 mesh sieve, and dried at 60 ° C for 2 hours to dry the granules. After 40 mesh (particle size 380 ⁇ m) sieve, the granules after the granulation were obtained.
  • the prescribed amount of cycloserine was passed through a 100 mesh sieve, and then mixed with the granulated auxiliary material, and the No. 1 gelatin hollow capsule was filled in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.814%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% at pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounts for 64.1% of the total, the cycloserine content is 99.713%, the wet granulation auxiliary material is 60 mesh, the solvent is water, the binder accounts for 1.0% of the total, and the binder is hypromellose E5.
  • the capsule prepared by the above method had a loss on drying of 0.558%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the wet granulation auxiliary material was 60 mesh, the solvent was water, the binder accounted for 1.0% of the total, and the binder was hydroxypropylcellulose MF.
  • the capsule prepared by the above method had a loss on drying of 0.679%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% at pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the dry granulation auxiliary material was 60 mesh, the compressible auxiliary material accounted for 10% of the total amount, and the compressible auxiliary material was anhydrous lactose.
  • talc powder and anhydrous lactose were mixed and then dry granulated to prepare 60-mesh auxiliary granules.
  • the prescribed amount of cycloserine was passed through a 100 mesh sieve, and then mixed with the granulated auxiliary material, and the No. 1 gelatin hollow capsule was filled in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 1.215%, a disintegration time in water of 5 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the dry granulation auxiliary material was 60 mesh, the compressible auxiliary material accounted for 16% of the total amount, and the compressible auxiliary material was anhydrous lactose.
  • talc powder and anhydrous lactose were mixed and then dry granulated to prepare 60-mesh auxiliary granules.
  • the prescribed amount of cycloserine was passed through a 100 mesh sieve, and then mixed with the granulated auxiliary material, and the No. 1 gelatin hollow capsule was filled in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 1.153%, a disintegration time in water of 5 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the dry granulation auxiliary material was 60 mesh, the compressible auxiliary material accounted for 10% of the total, and the compressible auxiliary material was starch.
  • talc powder and starch were mixed and then dry granulated to prepare 60-mesh auxiliary granules.
  • the prescribed amount of cycloserine was passed through a 100 mesh sieve, and then mixed with the granulated auxiliary material, and the No. 1 gelatin hollow capsule was filled in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 1.589%, a disintegration time in water of 5 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • Cycloserine accounted for 64.1% of the total, and the content of cycloserine was 99.713%.
  • the cyclic serine was co-granulated with the auxiliary materials by 60 mesh, and the amount of compressible auxiliary materials accounted for 0% of the total.
  • the prescribed amount of cycloserine is passed through a 100 mesh sieve, mixed with talc powder, and then dry granulated to prepare 60-mesh granules, and then the granulated granules are filled with gelatin hollow capsules of No. 1 gelatin capsules per capsule containing 250 mg of cycloserine. .
  • the capsule prepared by the above method had a loss on drying of 0.637%, a disintegration time in water of 14 minutes, and a dissolution rate of less than 70% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the cycloserine and the auxiliary materials together dried granulation 60 mesh, the compressive auxiliary materials accounted for 10% of the total, and the compressible auxiliary material was anhydrous lactose.
  • cycloserine was passed through a 100 mesh sieve, mixed with talc powder and anhydrous lactose, and then granulated by dry granulation to prepare granules of 60 mesh, and the granulated granules were filled in a capsule containing 250 mg of cycloserine per capsule. No. gelatin hollow capsule.
  • the capsule prepared by the above method had a loss on drying of 0.985%, a disintegration time in water of 9 minutes, and a dissolution rate of more than 85% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the cycloserine and the auxiliary materials together dried granulation 60 mesh, the compressive auxiliary materials accounted for 10% of the total, and the compressible auxiliary material was starch.
  • cycloserine is passed through a 100 mesh sieve, mixed with talc powder and starch, and then dry granulated to prepare 60-mesh granules, and then the granulated granules are filled with gelatin No. 1 in a capsule containing 250 mg of cycloserine per capsule. Hollow capsules.
  • the capsule prepared by the above method had a loss on drying of 1.122%, a disintegration time in water of 12 minutes, and a dissolution rate of less than 85% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, and the cycloserine was wet-granulated with the excipients by 60 mesh.
  • the solvent was ethanol, and the binder amounted to 0% of the total amount.
  • the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and then an appropriate amount of soft material made of ethanol is added, and the wet granules are sieved through 40 mesh, dried at 60 ° C for 2 hours, and the dried granules are passed through 60 mesh.
  • the granules were sieved, and the granulated granules were filled with No. 1 gelatin hollow capsules according to the specification of 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.667%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • the cyclic serine accounted for 64.1% of the total, the cycloserine content was 99.713%, the cycloserine was wet granulated with the excipients by 60 mesh, the solvent was ethanol, the binder amounted to 1.0% of the total amount, and the binder was polyvinylpyrrolidone K30.
  • the prescribed amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and then the prepared polyvinylpyrrolidone K30 ethanol solution is added and stirred.
  • the soft material is made, and the wet granules are sieved through 40 mesh, dried at 60 ° C for 2 h, and then the dried granules are sieved through 60 mesh, and the granulated granules are in the form of 250 mg of cycloserine per capsule. Fill the No. 1 gelatin hollow capsule.
  • the capsule prepared by the above method had a loss on drying of 0.784%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • Cycloserine accounted for 64.1% of total, cycloserine content was 99.713%, cycloserine was mixed with excipients for fluidized bed granulation of 60-80 mesh, solvent was ethanol, binder content was 1.0% of total, and binder was polyvinylpyrrolidone. K30.
  • the prescribed amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is prepared. After passing through a 100 mesh sieve, it is mixed with talc powder, and placed in a fluidized bed, sprayed with polyvinylpyrrolidone K30 ethanol solution to make wet granules, and dried in a fluidized state. After 60 mesh to 80 mesh sieve granules, The granulated granules were filled with No. 1 gelatin hollow capsules in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.532%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • Cycloserine accounted for 64.1% of total, cycloserine content was 99.713%, cycloserine was mixed with excipients for fluidized bed granulation of 60-80 mesh, solvent was ethanol, binder content accounted for 6.0% of total, and binder was polyvinylpyrrolidone. K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and placed in a fluidized bed to spray polyvinylpyrrolidone K30 ethanol solution.
  • the granules were wetted and dried in a fluidized state, and the granules were sieved through a 60-mesh to 80-mesh sieve, and the granulated granules were filled with a No. 1 gelatin hollow capsule in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.661%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% at pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • Cycloserine accounted for 64.1% of total, cycloserine content was 99.713%, cycloserine was mixed with excipients for fluidized bed granulation of 60-80 mesh, solvent was water, binder was 1.0% of total, and binder was polyvinylpyrrolidone. K30.
  • the prescribed amount of polyvinylpyrrolidone K30 is placed in an aqueous solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and placed in a fluidized bed to be sprayed with polyvinylpyrrolidone K30 aqueous solution to be wet.
  • the granules are dried in a fluidized state, and the granules are sieved through 60 mesh to 80 mesh, and the pellets after granulation are filled with gelatin hollow capsule No. 1 in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method has a loss on drying of 0.620%, a disintegration time in water of 4 minutes, and a pH of 1.2, pH 4.0, The dissolution rate at pH 6.8 and 15 minutes in water was greater than 90%.
  • Cycloserine accounted for 64.1% of total, cycloserine content was 99.713%, cycloserine was mixed with excipients for fluidized bed granulation of 60-80 mesh, solvent was ethanol, binder was 3.0% of total, and binder was polyvinylpyrrolidone. K30, gelatin hollow capsules have a loss on drying of 13.6%.
  • the prescription amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and placed in a fluidized bed to spray polyvinylpyrrolidone K30 ethanol solution.
  • the granules were wetted and dried in a fluidized state, and the granules were sieved through a 60-mesh to 80-mesh sieve, and the granulated granules were filled with a No. 1 gelatin hollow capsule in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.568%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • Cycloserine accounted for 64.1% of total, cycloserine content was 99.713%, cycloserine was mixed with excipients for fluidized bed granulation of 60-80 mesh, solvent was ethanol, binder was 3.0% of total, and binder was polyvinylpyrrolidone. K30, gelatin hollow capsules have a loss on drying of 16.8%.
  • the prescription amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and placed in a fluidized bed to spray polyvinylpyrrolidone K30 ethanol solution.
  • the granules were wetted and dried in a fluidized state, and the granules were sieved through a 60-mesh to 80-mesh sieve, and the granulated granules were filled with a No. 1 gelatin hollow capsule in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.699%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • Cycloserine accounted for 64.1% of total, cycloserine content was 99.713%, cycloserine was mixed with excipients for fluidized bed granulation of 60-80 mesh, solvent was ethanol, binder was 3.0% of total, and binder was polyvinylpyrrolidone. K30, hypromellose hollow capsules had a loss on drying of 2.2%.
  • the prescription amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and placed in a fluidized bed to spray polyvinylpyrrolidone K30 ethanol solution. Wet the granules and dry them in a fluidized state. After granulating through 60 mesh to 80 mesh, the granulated granules are filled with No. 1 hypromellose hollow capsules according to the specification of 250 mg of cycloserine per capsule. .
  • the capsule prepared by the above method had a loss on drying of 0.762%, a disintegration time in water of 8 minutes, and a dissolution rate of more than 85% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • Cycloserine accounted for 64.1% of total, cycloserine content was 99.713%, cycloserine was mixed with excipients for fluidized bed granulation of 60-80 mesh, solvent was ethanol, binder content was 1.0% of total, and binder was polyvinylpyrrolidone. K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and placed in a fluidized bed to spray polyvinylpyrrolidone K30 ethanol solution.
  • the granules were wetted and dried in a fluidized state, and the granules were sieved through a 60-mesh to 80-mesh sieve, and the granulated granules were filled with a No. 1 gelatin hollow capsule in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.676%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% at pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • Cycloserine accounted for 64.1% of total, cycloserine content was 99.668%, cycloserine was mixed with excipients to form granules of 60-80 mesh, solvent was ethanol, binder was 1.0% of total, and binder was polyvinylpyrrolidone. K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and placed in a fluidized bed to spray polyvinylpyrrolidone K30 ethanol solution.
  • the granules were wetted and dried in a fluidized state, and the granules were sieved through a 60-mesh to 80-mesh sieve, and the granulated granules were filled with a No. 1 gelatin hollow capsule in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.804%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • Cycloserine accounted for 64.1% of the total, and the content of cycloserine was 99.619%.
  • the cycloserine was mixed with the excipients to make 60-80 mesh fluidized bed.
  • the solvent was ethanol, the binder was 1.0% of the total amount, and the binder was polyvinylpyrrolidone. K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and placed in a fluidized bed to spray polyvinylpyrrolidone K30 ethanol solution.
  • the granules were wetted and dried in a fluidized state, and the granules were sieved through a 60-mesh to 80-mesh sieve, and the granulated granules were filled with a No. 1 gelatin hollow capsule in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.758%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% at pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • Cycloserine accounted for 64.1% of the total, and the content of cycloserine was 99.474%.
  • the cycloserine was mixed with the auxiliary material in the fluidized bed to make 60-80 mesh, the solvent was ethanol, the binder content was 1.0%, and the binder was polyvinylpyrrolidone. K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and placed in a fluidized bed to spray polyvinylpyrrolidone K30 ethanol solution.
  • the granules were wetted and dried in a fluidized state, and the granules were sieved through a 60-mesh to 80-mesh sieve, and the granulated granules were filled with a No. 1 gelatin hollow capsule in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.692%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8 and water for 15 minutes.
  • Cycloserine accounted for 64.1% of total, cycloserine content was 99.713%, cycloserine was mixed with excipients for fluidized bed granulation of 60-80 mesh, solvent was ethanol, binder content was 1.0% of total, and binder was polyvinylpyrrolidone. K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and placed in a fluidized bed to spray polyvinylpyrrolidone K30 ethanol solution.
  • the granules were wetted and dried in a fluidized state, and the granules were sieved through a 60-mesh to 80-mesh sieve, and the granulated granules were filled with a No. 1 gelatin hollow capsule in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.637%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • Cycloserine accounted for 64.1% of total, cycloserine content was 99.713%, cycloserine was mixed with excipients for fluidized bed granulation of 60-80 mesh, solvent was ethanol, binder content was 1.0% of total, and binder was polyvinylpyrrolidone. K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and placed in a fluidized bed to spray polyvinylpyrrolidone K30 ethanol solution.
  • the granules were wetted and dried in a fluidized state, and the granules were sieved through a 60-mesh to 80-mesh sieve, and the granulated granules were filled with a No. 1 gelatin hollow capsule in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.741%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • Cycloserine accounted for 64.1% of total, cycloserine content was 99.713%, cycloserine was mixed with excipients for fluidized bed granulation of 60-80 mesh, solvent was ethanol, binder content was 1.0% of total, and binder was polyvinylpyrrolidone. K30.
  • the prescription amount of polyvinylpyrrolidone K30 is configured as an ethanol solution of polyvinylpyrrolidone K30, and the prescribed amount of cycloserine is passed through a 100 mesh sieve, and then mixed with talc powder, and placed in a fluidized bed to spray polyvinylpyrrolidone K30 ethanol solution.
  • the granules were wetted and dried in a fluidized state, and the granules were sieved through a 60-mesh to 80-mesh sieve, and the granulated granules were filled with a No. 1 gelatin hollow capsule in a capsule containing 250 mg of cycloserine per capsule.
  • the capsule prepared by the above method had a loss on drying of 0.608%, a disintegration time in water of 4 minutes, and a dissolution rate of more than 90% in pH 1.2, pH 4.0, pH 6.8, and water for 15 minutes.
  • the pharmaceutical composition prepared by the embodiment of the invention can be applied to the preparation of a medicament for treating tuberculosis caused by Mycobacterium tuberculosis. It can also be applied to the preparation of a medicament for treating psychosis, depression, Alzheimer's disease or chronic pain.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Inorganic Chemistry (AREA)

Abstract

La présente invention concerne une composition pharmaceutique, un procédé de préparation associé et une application associée. La composition pharmaceutique est constituée de cyclosérine et d'un adjuvant, le diamètre de particule D90 de la composition pharmaceutique étant de 75 à 380 μm et la quantité de l'adjuvant représentant de 9 à 45 % de la composition pharmaceutique. La stabilité de la composition pharmaceutique selon l'invention est considérablement meilleure.
PCT/CN2015/100130 2015-12-22 2015-12-31 Composition pharmaceutique, procédé de préparation associé et application associée WO2017107242A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201510982014.2A CN105476976B (zh) 2015-12-22 2015-12-22 药物组合物及其制备方法和应用
CN201510982014.2 2015-12-22

Publications (1)

Publication Number Publication Date
WO2017107242A1 true WO2017107242A1 (fr) 2017-06-29

Family

ID=55664495

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2015/100130 WO2017107242A1 (fr) 2015-12-22 2015-12-31 Composition pharmaceutique, procédé de préparation associé et application associée

Country Status (2)

Country Link
CN (1) CN105476976B (fr)
WO (1) WO2017107242A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020052620A1 (fr) * 2018-09-13 2020-03-19 Syneurx International (Taiwan) Corp. Sels de composés de cyclosérine et applications associées
US11291654B2 (en) 2018-09-13 2022-04-05 Syneurx International (Taiwan) Corp. Formulations of cycloserine compounds and applications thereof
CN115177593A (zh) * 2022-08-08 2022-10-14 锦州奥鸿药业有限责任公司 一种谷氨酰胺颗粒剂及其制备方法

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107320471B (zh) * 2017-08-08 2020-10-09 湖南慧泽生物医药科技有限公司 一种治疗结核病的环丝氨酸药物组合物及其应用
CN107308147B (zh) * 2017-08-08 2020-09-18 新乡医学院第一附属医院 氨甲苯酸组合物在治疗结核病中的应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008118785A2 (fr) * 2007-03-23 2008-10-02 Tikvah Therapeutics Procédés de traitement de la dépression utilisant des traitements à effet immédiat et la d-cyclosérine

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT1073432E (pt) * 1998-04-14 2007-10-22 Gen Hospital Corp Utilização da d-alanina ou da d-serina para o tratamento da esquizofrenia
RU2248205C1 (ru) * 2003-09-18 2005-03-20 Открытое акционерное общество "Щелковский витаминный завод" Лекарственное средство в виде желатиновой капсулы
CN101254169A (zh) * 2006-04-04 2008-09-03 济南康泉医药科技有限公司 含抗结核病药物的缓释剂
RU103473U1 (ru) * 2010-11-17 2011-04-20 Раджеш Шарма Фармацевтическая капсула противотуберкулезного действия

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008118785A2 (fr) * 2007-03-23 2008-10-02 Tikvah Therapeutics Procédés de traitement de la dépression utilisant des traitements à effet immédiat et la d-cyclosérine

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020052620A1 (fr) * 2018-09-13 2020-03-19 Syneurx International (Taiwan) Corp. Sels de composés de cyclosérine et applications associées
US11291654B2 (en) 2018-09-13 2022-04-05 Syneurx International (Taiwan) Corp. Formulations of cycloserine compounds and applications thereof
CN115177593A (zh) * 2022-08-08 2022-10-14 锦州奥鸿药业有限责任公司 一种谷氨酰胺颗粒剂及其制备方法
CN115177593B (zh) * 2022-08-08 2023-08-25 锦州奥鸿药业有限责任公司 一种谷氨酰胺颗粒剂及其制备方法

Also Published As

Publication number Publication date
CN105476976A (zh) 2016-04-13
CN105476976B (zh) 2018-09-25

Similar Documents

Publication Publication Date Title
JP6560289B2 (ja) 新たな医薬組成物
WO2017107242A1 (fr) Composition pharmaceutique, procédé de préparation associé et application associée
WO2017140254A1 (fr) Composition pharmaceutique contenant un inhibiteur de janus kinase (jak) ou un sel pharmaceutiquement acceptable de celui-ci
WO2020249001A1 (fr) Comprimé solide pour voie orale comprenant un inhibiteur de tyrosine kinase de bruton et son procédé de préparation
CN108066319B (zh) 一种枸橼酸托法替布肠溶缓释微丸及其制备方法
WO2021129735A1 (fr) Préparation solide, son procédé de préparation et son utilisation
WO2022012172A1 (fr) Composition orale à libération prolongée pour un médicament insoluble, et son procédé de préparation
WO2006080481A1 (fr) Preparation multidose a liberation prolongee pour administration par voie orale et procede de production de celle-ci
CN102091051B (zh) 一种别嘌醇双释放制剂及其制备方法
KR20120094882A (ko) 모사프리드 또는 이의 염을 포함하는 서방형 약학 조성물
WO2019151405A1 (fr) Comprimés et leur procédé de production
WO2016000608A1 (fr) Dispersion solide d'allisartan isoproxil et composition pharmaceutique en contenant
JP2017190325A (ja) 化学的な安定性を改善した、非晶質体ソリフェナシン含有製剤
WO2020055364A2 (fr) Composition pharmaceutique comprenant de l'eltrombopag olamine
JP6680297B2 (ja) 経口投与用医薬組成物
EP3485877A1 (fr) Granule à libération prolongée avec du chlorhydrate de tamsulosine.
JP2017075139A (ja) 低用量薬物を含有する口腔内崩壊錠
CN113908153B (zh) 一种布瓦西坦药物组合物、其制备方法及应用
JP2020183382A (ja) フィンゴリモド塩酸塩含有製剤及びフィンゴリモド塩酸塩含有製剤の製造方法
JP2015063570A (ja) 口腔内崩壊錠
WO2014096983A1 (fr) Compositions pharmaceutiques stables de saxagliptin ou des sels de celui-ci
WO2024125654A1 (fr) Composition d'épalrestat à libération prolongée, son procédé de préparation et son utilisation
JP5563371B2 (ja) クエチアピンフマル酸塩含有経口用錠剤
JP6707471B2 (ja) ピロールカルボキサミドの固形組成物
CN104306346A (zh) 一种布南色林的缓释制剂及其制备方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15911238

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15911238

Country of ref document: EP

Kind code of ref document: A1